Severe COVID-19 induces autoantibodies against angiotensin II that correlate with blood pressure dysregulation and disease severity

  1. Priscilla S. Briquez
  2. Sherin J. Rouhani
  3. Jovian Yu
  4. Athalia R. Pyzer
  5. Jonathan Trujillo
  6. Haley L. Dugan
  7. Christopher T. Stamper
  8. Siriruk Changrob
  9. Anne I. Sperling
  10. Patrick C. Wilson
  11. Thomas F. Gajewski
  12. Jeffrey A. Hubbell
  13. Melody A. Swartz

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Abstract

Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can experience life-threatening respiratory distress, blood pressure dysregulation, and thrombosis. This is thought to be associated with an impaired activity of angiotensin-converting enzyme 2 (ACE2), which is the main entry receptor of SARS-CoV-2 and which also tightly regulates blood pressure by converting the vasoconstrictive peptide angiotensin II (AngII) to a vasopressor peptide. Here, we show that a significant proportion of hospitalized patients with COVID-19 developed autoantibodies against AngII, whose presence correlates with lower blood oxygenation, blood pressure dysregulation, and overall higher disease severity. Anti-AngII antibodies can develop upon specific immune reaction to the SARS-CoV-2 proteins Spike or receptor-binding domain (RBD), to which they can cross-bind, suggesting some epitope mimicry between AngII and Spike/RBD. These results provide important insights on how an immune reaction against SARS-CoV-2 can impair blood pressure regulation.

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  1. Version published to 10.1126/sciadv.abn3777
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    SciScore for 10.1101/2021.11.02.21265789: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

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    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.11.02.21265789v1 on medRxiv